Interleukin-1 receptor antagonist prevents embryonic implantation by a direct effect on the endometrial epithelium
Interleukin-1 receptor antagonist prevents embryonic implantation by a direct effect on the endometrial epithelium
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DOI：
10.1016/s0015-0282(98)00275-1
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发表时间：
1998-11-01
影响因子：
6.7
通讯作者：
Polan, ML
中科院分区：
文献类型：
--
作者：
Simón, C;Valbuena, D;Polan, ML
目的：研究白细胞介素 1 受体拮抗剂 (IL-1ra) 抗着床作用的胚胎和/或子宫内膜分子机制。设计：对照实验。环境：斯坦福大学的动物设施以及 Valenciano de Infertilidad 和悉尼大学的实验室。动物：12 周龄的 B6C3F-1 雌性小鼠。干预：腹腔注射重组人 IL-1ra主要结果指标：植入部位、胚胎形态和活力。 IL-1ra 治疗组动物与对照动物组中整合素和细胞外基质的聚合酶链反应和免疫组织化学分析以及子宫内膜的透射电子显微镜检查。结果：对照组和注射 IL-1ra 动物的妊娠率分别为 60% 和 13%。怀孕第 8 天，治疗组获得的子宫套管产生了 32 个囊胚。六只假孕动物接受 IL-1ra 处理的囊胚（左角）和对照囊胚（战斗角），结果 1 只怀孕，左右角分别有 2 个胚胎和 1 个胚胎。在妊娠第 4 天，IL-1ra 通过聚合酶链式反应下调 α4 mRNA。免疫组织化学显示α 4、α v 和β 3 减少，透射电子显微镜显示质膜转化受到抑制，结论：由于α 4、α v 和β 3 下调，IL-1ra 对胚胎粘附的损害是通过直接影响植入时上皮质膜的转化来介导的。(Fertil Steril(R) 1998:70:896-906。(C) 1998 年美国生殖医学会。）。
Objective: To investigate the embryonic and/or endometrial molecular mechanisms underlying the antiimplantation effect of interleukin-1 receptor antagonist (IL-1ra).Design: Controlled experiment.Setting: Animal facilities at Stanford University and laboratories of the Institute Valenciano de Infertilidad and the University of Sydney.Animal(s): Twelve-week-old B6C3F-1 female mice.Intervention(s): Intraperitoneal injections of recombinant human IL-1ra during the periimplantation period.Main Outcome Measure(s): Implantation sites, embryonic morphology, and viability. Polymerase chain reaction and immunohistochemistry for integrins and extracellular matrices and transmission electron microscopy of Endometrium in IL-1ra-treated versus control animals.Result(s): Pregnancy rates in control and IL-1ra-injected animals were 60% and 13%, respectively. At day 8 of pregnancy, Bushing of uteri obtained from the treated group resulted in 32 blastocysts. Six pseudopregnant animals received IL-1ra-treated blastocysts (left horn) and control blastocysts (fight horn), resulting in one pregnancy, with two embryos and one embryo in the left and right horns, respectively. At day 4 of pregnancy, IL-1ra down-regulated alpha 4 mRNA with use of the polymerase chain reaction. Immunohistochemistry showed a decrease of alpha 4, alpha v, and beta 3, and transmission electron microscopy revealed inhibition of transformation of the plasma membrane,Conclusion(s): Impairment of embryonic adhesion with IL-1ra is mediated through a direct effect on transformation of the epithelial plasma membrane at the time of implantation as a result of down-regulation of alpha 4, alpha v, and beta 3. (Fertil Steril(R) 1998:70:896-906. (C) 1998 by American Society for Reproductive Medicine.).